The 2013 guidelines issued by the American Association of Clinical Endocrinologists and the American Thyroid Association reiterated their long standing opinion that only a single hormone, T4 (Synthroid, levothyroxine) is advised for treatment of hypothyroidism. These key organizations
Every so often I like to bring attention to someone who has struggled to get properly treated for hypothyroidism. Not everyone shares the same dilemma regarding treatment of hypothyroidism because T4 by itself may be sufficient in many instances. But for those who continue to experience symptoms of hypothyroidism despite T4 treatment, adding T3 can be a life changing experience.
Here is Sarah’s story:
I was diagnosed with hypothyroidism in my early twenties and Synthroid did not help. I did not know at the time that many of my symptoms were due to hypothyroidism. After changing to my long time physician, I told her of my original diagnosis some years back. She did only the TSH and told me I was no longer hypothyroid! So for some 15 years after being in her care and continuing to feel crummy, then for the last 8 steadily gaining weight and feeling worse, I was not on any medication. I begged her for Cytomel several years back and was denied…she said she didn’t treat with that. When I finally was deemed hypo by her, she put me on the smallest dose of levothyroxine. It did not help. I finally went to see a shrink and he put me on 25 mcg of Cytomel. For the first time in my post pubescent life, I feel like living. My dose was upped to 50, and I felt even better but my thyroid levels were off, so we are now working on that and I am back to 25 mcg per day. If you can’t get Cytomel from your regular physician, you might get a psychiatrist to prescribe it. It changed my life and I finally feel alive. I’ve since switched primary physician because she wouldn’t listen to me, and she didn’t like that I was on Cytomel. I don’t know what it is about this medication that regular physicians don’t like and make them refuse to treat with it, especially when so many can benefit from it. I’ve lost only 12 lbs since being on it, but I gained nearly 35 unnecessarily while not being properly treated and was told to eat less and exercise more…I only ate about 1500 calories a day and walked my dog 2 miles each day, so I don’t feel it had anything to do with my diet!
As a culture we don’t plan for a sudden halt in scientific advancements. Our tendency is to expect progress to be rapid and continuous. My prediction is that in certain areas of medical science we are likely to see not only a halt in progress but a slipping backward. In particular, the realm of medical weight management is in complete disarray at this time. Two new drugs designed to induce weight loss have been shot down by the FDA in the last few months. The first is Qnexa, developed by Vivus Inc. Interestingly, Qnexa combines two drugs already approved for use in the U.S. One of the drugs is phentermine which is a medication used for decades as an appetite suppressant. The other is a common drug used to treat seizures with the brand name Topamax (topiramate) which also induces weight loss. The drug performed admirably in clinical trials with most participants losing over 10% of body mass. The FDA cited excessive risks of the drug in its statement of rejection. One wonders why the drugs are still being marketed separately if they are so dangerous.
The latest drug to be rejected by the FDA is Lorgess (lorcaserin), developed by Arena Pharmaceuticals. This drug, not as effective as Qnexa, produced 5% body mass loss in about half of participants in clinical trials. Lab animals showed a tendency to develop breast tumors when exposed to the medication, adding to the FDA’s decision to reject the drug application based on safety concerns.
I am a strong advocate of drug safety and regulation. On the other hand we know obesity, and with it Type 2 diabetes, is epidemic in the U.S. I regard weight loss as the “holy grail” when treating type 2 diabetes and yet it is the most difficult goal to achieve. Any drug which could assist in weight loss is highly desirable in the treatment of Type 2 diabetes. Not only does blood sugar improve with weight loss but also blood pressure and cholesterol readings show declines. All three of these parameters are known to be prime contributors to the main cause of death in diabetics, cardiovascular disease.
It has already been 10 years since the last drug was approved specifically for a weight loss indication. The failure of these two latest medications to achieve approval is certain to cause the pharmaceutical industry to severely curtail if not abandon further investment in this type of drug development.
Why is the FDA so reluctant to approve a weight loss pill? This is a complex issue but requires an answer. A new weight loss inducing medication is certain to be highly anticipated and widely prescribed. Therefore, from the very first day of approval the FDA must take responsibility for the well being of millions of people who are likely to take the medication. We are a society which demands our medications deliver miraculous cures with no side-effects. If someone perceives they have been injured by a medication our legal system is primed to unleash brutal retribution on everyone remotely involved in the approval process. Abuse and injury with a medication designed to cause weight loss is almost a certainty. This is a no-win situation for the administration of the FDA.
I predict it will be at least another 10 years before a medication for weight loss is approved by the FDA. Unless there is a change in the climate of litigation in this country it will take longer than that. In the meantime the only new developments in weight loss drugs will be the result of exploiting appetite suppressant effects which are the “side-effect” of medications approved for other purposes.
Gary Pepper, M.D.
Due to the potential for abuse and high cost, growth hormone treatment in adults is the subject of much controversy. I believe that treating adults with growth hormone deficiency is many times an appropriate and beneficial choice. Firming up my conviction for treating adult growth hormone deficiency is a recent study conducted in the Netherlands and UK published in the Journal of Endocrinology and Metabolism (JCEM 95:3664-3674, 2010). The researchers compared Body Mass Index (BMI), waist circumference, triglycerides, and HDL (good cholesterol), between normal adults and those with low growth hormone levels due to deficient pituitary function (hypopituitarism). All measurements of obesity and lipid metabolism were significantly worse in the young adults (younger than 57 years) with growth hormone deficiency compared to normal adults of a similar age.
As I pointed out in previous articles at metabolism.com, growth hormone levels naturally decline as we get older. The authors of the present study note that growth hormone levels decline 14% per decade in adults. I conceive of this as one of the ways nature gets rid of us after we complete our biological/reproductive functions, since without growth hormone our muscles, immune and nervous systems, decline, leading to death. It’s planned obsolescence… what is typically referred to as aging. In the recent study senior citizens have equivalent levels of obesity and abnormal lipid metabolism as young adults with growth hormone deficiency. The authors note the effect on the body of growth hormone deficiency in young adults is equivalent to 40 years of aging. The theory that growth hormone functions to preserve our tissues during youth and aging results from its absence, appears confirmed by these results.
Most normal young adults aren’t growth hormone deficient and the population that would qualify for growth hormone treatment from this group is small. What about older adults with low growth hormone who are troubled by the “natural” decline in their body function? Should or could we treat this much larger population with growth hormone? It is my experience that private and federal insurers will not pay for this treatment regarded as “cosmetic”. On the other hand, there will be physicians who will comply with a request for growth hormone treatment from individuals who possess enough cash and motivation. Less affluent or determined individuals will have to contend with natural aging just as our ancestors have done for thousands of years.
This information is for educational purposes only and is not intended as medical advice or treatment.
Gary Pepper, M.D.
A patient advocacy group in the UK is fighting for recognition of combination therapy (t4 plus t3) to treat hypothyroidism (low thyroid levels). They are asking for people who have benefited from combination therapy to visit their website and demonstrate their support for this form of treatment. Why not have a look and decide for yourself?
Here is the contact info:
Please will you post the following link to the very short questionnaire , and urge those members who remained ill on T4 only, yet fared better with a T3 hormone product (either synthetic or natural) to take part.
All responses will be collated automatically online.
Thyroid Patient Advocate
The adrenal glands sitting on top of the kidneys make several hormones critical to life. The central part of the adrenal makes the hormone we refer to as adrenalin, technically from the group known as catecholamines. This is the stress responsive hormone causing rapid heart rate, sweating, increased mental alertness, preparing the body for “fight or flight”. The outer portion of the adrenal makes the hormone cortisol, also known as cortisone. Cortisol maintains, among other things, the blood pressure, fluid and salt balance. Without sufficient cortisol production by the adrenals, life cannot be sustained. What is surprising is that excess cortisol can be as harmful to health as insufficient cortisol.
Deficient cortisol production is referred to as adrenal insufficiency (Addison’s disease is one form of this), while excess adrenal function is termed Cushing’s Syndrome. During certain types of stress such as severe infection the adrenal gland can produce up to 10 times the normal amount of cortisol. If cortisol levels remain elevated for prolonged periods of time the hormone’s destructive nature is revealed by the break down of soft tissue such as skin and muscle and weakening of the immune system with frequent and aggressive infections occurring sometimes with fatal outcome. Heart disease has not been associated with high cortisol levels until a recent study suggested this possibility.
Researchers from the U.K. examined morning cortisol levels in 1066 men and women with Type 2 diabetes participating in the Edinburgh Type 2 Diabetes Study. A positive relationship was discovered between cortisol levels and the occurrence of heart disease such as heart attack and angina. The higher the cortisol levels were the greater the risk of heart disease. Cortisol levels in diabetics were found to be higher than in non-diabetics, in general. The researchers could not explain why the cortisol levels caused heart disease or why levels were higher in diabetics. (From the April edition of the Journal of Clinical Endocrinology and Metabolism 95:1602-1608).
‘Adrenal fatigue’ is a recently proposed diagnosis used to explain a variety of general symptoms such as fatigue, moodiness, muscle aches, and diminished mental function. Supposedly, adrenal fatigue results from mild impairment of cortisol production. Practitioners who diagnose “adrenal fatigue” are prescribing synthetic versions of cortisol as treatment. The possibility of heart disease resulting from excess cortisol should be a factor that patients and medical professionals must consider before embarking on adrenal “supplementation” programs.
This information is for educational purposes only and is not intended as medical advice or treatment.
Gary Pepper, M.D.
Treatment of hypothyroidism (low thyroid function) is accomplished by administering thyroid hormone by mouth in sufficient amounts to restore levels back to normal. At first glance this might seem like a simple goal to achieve. The truth is hormone replacement therapy is complex because there exists two very different thyroid hormones and because levels of thyroid hormone in the blood do not always reflect the amount of thyroid hormone within the cells where the hormone exerts its effects. In Part One of this blog I began to discuss how genetic differences among individuals could explain why some people need a complex mix of thyroid hormones to adequately treat hypothyroidism. In Part 2, I want to explain the nature of the differences between individuals and how it determines what sort of thyroid hormone therapy may be needed.
In May 2009 a group of researchers (Panicker, V. et al) in the UK published the WATTS study, the largest and most comprehensive study to date, of hypothyroid patients treated with combination t4 and t3. The goal of the study was to discover whether genetic differences in the population of hypothyroid patients accounts for some individuals needing t3 in addition to traditional t4 therapy. The researchers looked at 697 hypothyroid individuals and analyzed their DNA for differences in the portions controlling crucial enzymes which process thyroid hormones known as deiodinases. These enzymes are found widely distributed in the body including the thyroid, brain, muscle, liver, kidney and pituitary gland. As explained above, deiodinases convert t4 to the much stronger form of thyroid hormone, t3. At the same time the researchers measured patients’ mood and sense of well being on t4 alone and when t3 was added to the therapy.
Key findings of the WATTS study are that there is a substantial difference among individuals in the genes that make the deiodinases. In other words, due to genetic differences (mutations), there are differences in the way individuals make t3 out of t4. In a group of people, mutations in the genes that make a particular protein (in this case, the deiodinase), are called polymorphisms. The researchers discovered that a certain mutation in the deiodinase gene is associated with a poor sense of well being on t4 only therapy, and in the presence of this mutation a significantly better response to adding t3 can be found compared to those without this mutation. Of the group of hypothyroid patients studied in the UK about 16% possessed the faulty deiodinase gene. In other groups in other countries the percentage of people with this mutation could be higher or lower.
The traditional treatment of hypothyroidism is to administer t4 (Synthroid, Levothyroxine, Levoxyl etc.). It is the conventional wisdom that inactive t4 is converted in the body to the active thyroid hormone t3 by “peripheral conversion” in sufficient amounts to restore normal thyroid balance. The recent breakthrough discoveries described in the WATTS study reveal for the first time that individuals differ in how their bodies process (metabolize) thyroid hormone. While some may convert enough t4 to t3 in the cells of the body to restore normal function, due to genetic differences some individuals will not be able to make enough t3 leaving them with persistent hypothyroid symptoms. Since the problem is a deficiency of t3 within the cells of the body, measuring thyroid hormone levels in the blood cannot adequately reveal the problem. T4 replacement treatment alone can result in thyroid levels that appear normal on blood tests so doctors conclude that persistent hypothyroid symptoms are not related to the hormone therapy.
Based on my personal experience and the documented experience of many of the members of Metabolism.com it is clear that endocrinologists and other physicians are often reluctant to consider combination therapy for hypothyroidism, either by using Armour thyroid or adding t3 (Cytomel, liothyronine) to t4 only therapy. With this new research in hand, hypothyroid individuals and their advocates can finally state with confidence that: Yes! There is a firm scientific foundation for combination t4/t3 therapy and; No! We are not just chronic complainers or kooks. If I had hypothyroidism and was going to request a change in my thyroid treatment I would say something like, “Due to polymorphism of the deiodinase gene I probably possess a defective D2 deiodinase and therefore my peripheral conversion of t4 to t3 is impaired. I need t3 added to t4 to compensate for reduced intracellular t3 levels which cannot be detected on blood tests. Without t3 I continue to suffer with cellular hypothyroidism which is the likely cause of my persistent symptoms.”
If you try this approach and your doctor looks bewildered hand them a copy of the study by Panicker et al in the Journal of Clinical Endocrinology and Metabolism, 2009, 94(5): 1623-1629.
Gary Pepper, M.D.
Notice: This article is for informational purposes only and does not substitute for the advice or treatment of your own physician. The disclaimer for all blogs at metabolism.com, applies.